Dataset Information

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

ABSTRACT:

Background/aims

This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test.

Methods

Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer's disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-?4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated.

Results

Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03).

Conclusion

The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.

SUBMITTER: Gifford KA

PROVIDER: S-EPMC6323369 | biostudies-literature | 2018 Sep-Dec

REPOSITORIES: biostudies-literature

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Publications

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

Gifford Katherine A KA Liu Dandan D Neal Jacquelyn E JE Babicz Michelle A MA Thompson Jennifer L JL Walljasper Lily E LE Wiggins Margaret E ME Turchan Maxim M Pechman Kimberly R KR Osborn Katie E KE Acosta Lealani Mae Y LMY Bell Susan P SP Hohman Timothy J TJ Libon David J DJ Blennow Kaj K Zetterberg Henrik H Jefferson Angela L AL

Dementia and geriatric cognitive disorders extra 20180901 3

<h4>Background/aims</h4>This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test.<h4>Methods</h4>Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (<i>n</i> = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (<i>n</i> = 111) underwent lumbar puncture for analysis of Alzheimer's dis ...[more]

PMID: 30631339

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Project description:Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid ?42 concentration in CSF from cognitively normal but not impaired participants. In dementia, altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its lost association with CSF amyloid ?42 concentration, underscores the potential of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for AD diagnosis and/or treatment.

Project description:Background: Hypertension is an important risk factor for Alzheimer's disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances. Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies. Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-β42, phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities. Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups. Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.

Dataset Information

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

Background/aims

Methods

Results

Conclusion

Publications

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

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